DEK promoted EMT and angiogenesis through regulating PI3K/AKT/mTOR pathway in triple-negative breast cancer.
DEK promoted EMT and angiogenesis through regulating PI3K/AKT/mTOR pathway in triple-negative breast cancer.
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DEK通过调节PI3K/AKT/mTOR通路促进三阴性乳腺癌EMT和血管生成
DOI：
10.18632/oncotarget.21864
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发表时间：
2017-11-17
期刊：
影响因子：
--
通讯作者：
Jin T
中科院分区：
文献类型：
--
作者：
Yang Y;Gao M;Lin Z;Chen L;Jin Y;Zhu G;Wang Y;Jin T
三阴性乳腺癌（TNBC）是与不良预后相关的高度侵袭性乳腺癌亚型。DEK作为一种癌基因，参与多种细胞代谢的调控，在肿瘤的生长和发展中起重要作用。越来越多的证据表明DEK的异常表达与多种恶性肿瘤的发生密切相关。然而，DEK可能参与上皮间质转化（EMT）和TNBC中的血管生成仍不清楚。在本研究中，我们发现DEK的过表达与TNBC的临床分期、分化程度和淋巴结（LN）转移显著相关，并表明TNBC患者的总体生存率较低。此外，我们证明，DEK耗竭可以显着减少细胞的增殖，迁移，侵袭和血管生成在体外。我们还发现DEK通过激活PI 3 K/AKT/mTOR通路促进癌细胞的血管生成和转移。此外，我们揭示了DEK耗竭对小鼠异种移植肿瘤模型中肿瘤生长和进展的抑制作用。这些数据表明，DEK通过PI 3 K/AKT/mTOR信号通路促进TNBC细胞增殖、血管生成和转移，因此，DEK可能是TNBC治疗的潜在靶点。
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer associated with poor prognosis. As an oncogene, DEK involves in regulation of various cellular metabolisms and plays an important role in tumor growth and progression. Increasing evidences suggested that abnormal expression of DEK is closely related to multiple malignant tumors. However, the possible involvement of DEK in epithelial to mesenchymal transition (EMT) and angiogenesis in TNBC remains unclear. In the present study, we revealed that the over-expression of DEK was significantly correlated with clinical stage, differentiation, and lymph node (LN) metastasis of TNBC and indicated poor overall survival of TNBC patients. Moreover, we demonstrated that DEK depletion could significantly reduce cell proliferation, migration, invasion and angiogenesis in vitro. We also found that DEK promoted cancer cell angiogenesis and metastasis by activating the PI3K/AKT/mTOR pathway. Furthermore, we revealed the inhibitory effect of DEK depletion on tumor growth and progression in a xenograft tumor model in mice. These data indicated that DEK promotes TNBC cell proliferation, angiogenesis, and metastasis via PI3K/AKT/mTOR signaling pathway, and therefore, it might be a potential target in TNBC therapy.
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影响因子：
--
作者：
Adams AK;Bolanos LC;Dexheimer PJ;Karns RA;Aronow BJ;Komurov K;Jegga AG;Casper KA;Patil YJ;Wilson KM;Starczynowski DT;Wells SI
通讯作者：
Wells SI
影响因子：
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作者：
Jiang, Bing-Hua;Liu, Ling-Zhi
通讯作者：
Liu, Ling-Zhi
影响因子：
14.9
作者：
Kavanaugh GM;Wise-Draper TM;Morreale RJ;Morrison MA;Gole B;Schwemberger S;Tichy ED;Lu L;Babcock GF;Wells JM;Drissi R;Bissler JJ;Stambrook PJ;Andreassen PR;Wiesmüller L;Wells SI
通讯作者：
Wells SI
Prrx1b 沉默可抑制三阴性乳腺癌中的细胞增殖、迁移、侵袭和上皮间质转化。
影响因子：
5.3
作者：
Lv ZD;Yang ZC;Liu XP;Jin LY;Dong Q;Qu HL;Li FN;Kong B;Sun J;Zhao JJ;Wang HB
通讯作者：
Wang HB
影响因子：
--
作者：
Massihnia D;Galvano A;Fanale D;Perez A;Castiglia M;Incorvaia L;Listì A;Rizzo S;Cicero G;Bazan V;Castorina S;Russo A
通讯作者：
Russo A